Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines.

Introduction: The correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification. Methods: Genetic samples were sourced from five cat breeds: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair. Allele frequencies were determined, and in the subset with phenotypes available, odds ratios to determine the association with HCM were calculated. In silico evaluation followed with joint evidence and data from other publications assisting in the classification of each variant. Results: Two variants, MYBPC3:c.91G > C [A31P] and MYBPC3:c.2453C > T [R818W], were designated as pathogenic. One variant, MYH7:c.5647G > A [E1883K], was found likely pathogenic, while the remaining three were labeled as variants of unknown significance. Discussion: Routine genetic testing is advised solely for the MYBPC3:c.91G > C [A31P] in the Maine Coon and MYBPC3:c.2453C > T [R818W] in the Ragdoll breed. The human ACMG guidelines serve as a suitable foundational tool to ascertain which variants to include; however, refining them for application in veterinary medicine might be beneficial.

Canine coat color E locus updates: Identification of a new MC1R variant causing 'sable' coat color in English Cocker Spaniels and a proposed update to the E locus dominance hierarchy.

The coat color phenotype 'sable' occurs in the English Cocker Spaniel dog breed. It closely resembles other canine color patterns known as domino/grizzle/pied (eA allele) and grizzle/domino (eG allele) determined by variants in the melanocortin 1 receptor gene (MC1R; 'extension' or E locus), a key multi-allele regulator of coat color. We examined genetic variation in MC1R, and found one new non-synonymous variant, c.250G>A (p.(Asp84Asn)), consistently associated with the English Cocker Spaniel 'sable' phenotype. We propose calling this newly identified allele eH and further show that the eA , eH and eG (previously known as EG ) alleles associate with similar phenotypes in dogs impacting genotypes regulated by beta-defensin 103 gene (CBD103; K locus) and agouti signaling protein gene (ASIP; A locus) in the absence of the EM and E alleles. This suggests that all three alleles are putative reduced-function variants of the MC1R gene. We propose the revised and updated E locus dominance hierarchy to be EM > E > eA /eH /eG > e1-3 .

The Bats of Greece: An Updated Review of Their Distribution, Ecology and Conservation.

Bats of Greece have been studied since the second half of the 19th century. Their distribution and ecology, however, remain poorly understood. Conservation efforts for the protection of the roosting and foraging habitats of their populations in Greece are limited. To date, 35 bat species have been recorded from Greece. Four species (Eptesicus anatolicus, Plecotus auritus, Myotis brandtii and Rousettus aegyptiacus) have a limited distribution in the country and the presence of one species (Myotis mystacinus) requires verification. The present study summarises all existing knowledge and adds several hundred new records on the distribution of bats of Greece. Additionally, it provides a summary of new insights on various aspects of their roosting ecology, foraging habitat use, altitudinal distribution, winter activity and landscape characteristics around major roosts. Finally, it discusses the current research and conservation needs of Greek bats.

Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.

Hundreds of genetic variants implicated in Mendelian disease have been characterized in dogs and commercial screening is being offered for most of them worldwide. There is typically limited information available regarding the broader population frequency of variants and uncertainty regarding their functional and clinical impact in ancestry backgrounds beyond the discovery breed. Genetic panel screening of disease-associated variants, commercially offered directly to the consumer or via a veterinary clinician, provides an opportunity to establish large-scale cohorts with phenotype data available to address open questions related to variant prevalence and relevance. We screened the largest canine cohort examined in a single study to date (1,054,293 representative dogs from our existing cohort of 3.5 million; a total of 811,628 mixed breed dogs and 242,665 purebreds from more than 150 countries) to examine the prevalence and distribution of a total of 250 genetic disease-associated variants in the general population. Electronic medical records from veterinary clinics were available for 43.5% of the genotyped dogs, enabling the clinical impact of variants to be investigated. We provide detailed frequencies for all tested variants across breeds and find that 57% of dogs carry at least one copy of a studied Mendelian disease-associated variant. Focusing on a subset of variants, we provide evidence of full penetrance for 10 variants, and plausible evidence for clinical significance of 22 variants, on diverse breed backgrounds. Specifically, we report that inherited hypocatalasia is a notable oral health condition, confirm that factor VII deficiency presents as subclinical bleeding propensity and verify two genetic causes of reduced leg length. We further assess genome-wide heterozygosity levels in over 100 breeds, and show that a reduction in genome-wide heterozygosity is associated with an increased Mendelian disease variant load. The accumulated knowledge represents a resource to guide discussions on genetic test relevance by breed.

Seasonal swarming behavior of Myotis bats revealed by integrated monitoring, involving passive acoustic monitoring with automated analysis, trapping, and video monitoring.

Bat abundance, diversity, and behavior can be monitored by capturing bats for identification and measurement in the hand, but this has several disadvantages. These include disturbance to the bats, which limits the frequency with which captures can be made at an individual capture site, and potentially alters the behaviors being studied. Infrared video monitoring, passive acoustic recording and automated analysis and identification of bat calls offers an alternative set of noninvasive methods for monitoring bats. In this study, we examine the effectiveness of acoustic monitoring in comparison with capture-based and video monitoring of seasonal swarming behavior among several species of Myotis bats in southern Britain. We applied these complementary approaches to describe seasonal, overnight, and species-specific variation in swarming behavior in a multispecies community of Myotis bats. We show that the three monitoring approaches have advantages and disadvantages for different tasks, but can be viewed as highly complementary methods for addressing different types of research questions. In our study of swarming behavior, capture and examination of bats in the hand was necessary for measuring sex ratios, reproductive status, and even for confirmation of species identification for some difficult to separate taxa. Capture is also an essential aspect of tagging bats for individual identification and tracking studies. Video monitoring is useful for understanding the behavior of bats at swarming sites, and measuring the flux of individuals into and out of roosting or swarming sites. Passive acoustic monitoring is a valuable noninvasive method for continuous monitoring of within-night, seasonal, and between-year variation in the abundance of bat calls. These can be used as an index of variation in relative abundance within-but not between-bat species.

Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.

In the largest DNA-based study of domestic cats to date, 11,036 individuals (10,419 pedigreed cats and 617 non-pedigreed cats) were genotyped via commercial panel testing elucidating the distribution and frequency of known disease, blood type, and physical trait associated genetic variants across cat breeds. This study provides allele frequencies for many disease-associated variants for the first time and provides updates on previously reported information with evidence suggesting that DNA testing has been effectively used to reduce disease associated variants within certain pedigreed cat populations over time. We identified 13 disease-associated variants in 47 breeds or breed types in which the variant had not previously been documented, highlighting the relevance of comprehensive genetic screening across breeds. Three disease-associated variants were discovered in non-pedigreed cats only. To investigate the causality of nine disease-associated variants in cats of different breed backgrounds our veterinarians conducted owner interviews, reviewed clinical records, and invited cats to have follow-up clinical examinations. Additionally, genetic variants determining blood types A, B and AB, which are relevant clinically and in cat breeding, were genotyped. Appearance-associated genetic variation in all cats is also discussed. Lastly, genome-wide SNP heterozygosity levels were calculated to obtain a comparable measure of the genetic diversity in different cat breeds. This study represents the first comprehensive exploration of informative Mendelian variants in felines by screening over 10,000 pedigreed cats. The results qualitatively contribute to the understanding of feline variant heritage and genetic diversity and demonstrate the clinical utility and importance of such information in supporting breeding programs and the research community. The work also highlights the crucial commitment of pedigreed cat breeders and registries in supporting the establishment of large genomic databases, that when combined with phenotype information can advance scientific understanding and provide insights that can be applied to improve the health and welfare of cats.

Elastic fibres in alcoholic liver disease.

The literature on the contribution of elastic fibre deposition to alcohol-related liver disease (ARLD) is limited. We studied: (1) 180 liver biopsies from ARLD patients; (2) 20 ARLD explant livers; (3) 213 liver biopsies with non-ARLD injury. Elastic fibres were assessed in terms of their distribution around hepatocytes [pericellular elastosis (PCE)] and within bridging fibrous septa (septal elastosis) and scored using a semiquantitative system. We also investigated the composition of the elastic fibres (oxytalan, elaunin and mature elastic fibres) in 20 cases. PCE was associated with steatohepatitis in ARLD patients and with ARLD when compared to non-ARLD cases (p < 0.001). Oxytalan fibres were identified in PCE in ARLD biopsies and broken dense perisinusoidal mature elastic fibres in explanted livers. Septal elastosis increased from intermediate to advanced fibrosis stage. Early septal elastosis contained oxytalan fibres, whereas septal elastosis at more advanced stages contained mainly mature elastic fibres. PCE is a typical feature of steatohepatitis in ARLD and includes oxytalan fibres. Septal elastosis is a gradual process with a transition from oxytalan to mature elastic fibres usually present in explanted livers. There may be different dynamics in the assembly and reabsorption of pericellular and septal elastic fibres, and a potential role for stratification of patients with advanced stage ARLD.

Evaluation of Personality Perception in Men Before and After Facial Cosmetic Surgery.

IMPORTANCE: Facial cosmetic surgery has previously focused on improvements in perceived physical attractiveness and youthfulness. However, human beings are judged throughout life based on many other characteristics and personal qualities that are conveyed by their faces. OBJECTIVE: To examine the association of facial cosmetic surgery in men with perceptions of attractiveness, masculinity, and personality traits. DESIGN, SETTING, AND PARTICIPANTS: Cohort study with retrospective evaluation by blinded raters of preoperative and postoperative photographs of 24 male patients who underwent facial cosmetic surgery between January 1, 2009, and January 31, 2016. A total of 6 surveys were constructed with 8 sets of photographs each (4 preoperative and 4 postoperative). Each of these surveys was then sent to at least 36 lay people via the web-based survey tool Survey Monkey. Additional invites were sent for individual surveys until a minimum of 24 responses were received for each survey. Preoperative and postoperative photographs of the same patient were not placed in the same survey to avoid recall bias. Anonymous raters used a 7-point Likert scale to rate their perception of each patient's personality traits (aggressiveness, extroversion, likeability, risk seeking, sociability, and trustworthiness), attractiveness, and masculinity based on photographs in their assigned survey. Raters were blinded to study intent. Data analysis was performed between August 2018 and March 2019. MAIN OUTCOMES AND MEASURES: Ratings of personality, attractiveness, and masculinity. RESULTS: This survey study included photographs of 24 men who underwent facial cosmetic surgery; the mean (SD) age of the patients was 49.3 (16.4) years. A total of 145 participants completed the survey; the majority of respondents were men (n = 81; 56%) between the ages of 25 and 34 years (n = 116; 80%). Score increases were significant for perceived attractiveness (0.29; 95% CI, 0.13-0.46), likeability (0.41; 95% CI, 0.24-0.57), social skills (0.25; 95% CI, 0.08-0.40), and trustworthiness (0.27, 95% CI, 0.11-0.44) when evaluating all facial cosmetic procedures together (upper blepharoplasty, lower blepharoplasty, face-lift, brow-lift, neck-lift, rhinoplasty, and/or chin implant). Upper blepharoplasty was associated with positive changes in perceived likeability (0.72; 95% CI, 0.06-1.50) and trustworthiness (0.74; 95% CI, 0.22-1.25). Lower blepharoplasty was associated with decreased perception of risk seeking (-0.78; 95% CI, -1.45 to -0.10). Face-lift was associated with increased perception of likeability (0.69; 95% CI, 0.08-1.30) and trustworthiness (0.66; 95% CI, 0.05-1.27). Neck-lift was associated with increased perception of extroversion (0.60; 95% CI, 0.10-1.09) and masculinity (0.70; 95% CI, 0.21-1.19). Patients who underwent rhinoplasty had improvements in perceived attractiveness (0.51; 95% CI, 0.03-1.00) and likeability (0.40; 95% CI, 0.03-1.00). Chin augmentation did not show any significant improvements. CONCLUSIONS AND RELEVANCE: The results of this study suggest that men undergoing facial cosmetic surgery may experience changes in perceived attractiveness, masculinity, and a variety of personality traits. These findings complement those from a previous study on female patients, which together broaden the understanding of the association of cosmetic surgery with societal perceptions of persona. LEVEL OF EVIDENCE: NA.

Correction: Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs.

[This corrects the article DOI: 10.1371/journal.pgen.1007361.].

Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs.

Knowledge on the genetic epidemiology of disorders in the dog population has implications for both veterinary medicine and sustainable breeding. Limited data on frequencies of genetic disease variants across breeds exists, and the disease heritage of mixed breed dogs remains poorly explored to date. Advances in genetic screening technologies now enable comprehensive investigations of the canine disease heritage, and generate health-related big data that can be turned into action. We pursued population screening of genetic variants implicated in Mendelian disorders in the largest canine study sample examined to date by examining over 83,000 mixed breed and 18,000 purebred dogs representing 330 breeds for 152 known variants using a custom-designed beadchip microarray. We further announce the creation of MyBreedData (www.mybreeddata.com), an online updated inherited disorder prevalence resource with its foundation in the generated data. We identified the most prevalent, and rare, disease susceptibility variants across the general dog population while providing the first extensive snapshot of the mixed breed disease heritage. Approximately two in five dogs carried at least one copy of a tested disease variant. Most disease variants are shared by both mixed breeds and purebreds, while breed- or line-specificity of others is strongly suggested. Mixed breed dogs were more likely to carry a common recessive disease, whereas purebreds were more likely to be genetically affected with one, providing DNA-based evidence for hybrid vigor. We discovered genetic presence of 22 disease variants in at least one additional breed in which they were previously undescribed. Some mutations likely manifest similarly independently of breed background; however, we emphasize the need for follow up investigations in each case and provide a suggested validation protocol for broader consideration. In conclusion, our study provides unique insight into genetic epidemiology of canine disease risk variants, and their relevance for veterinary medicine, breeding programs and animal welfare.

Detailed evaluation of one step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis and prediction of non-sentinel nodal involvement: experience from a London teaching hospital.

One step nucleic acid (OSNA) is a molecular diagnostic assay for intra-operative detection of sentinel node metastases. This study compared OSNA with standard histopathology in 283 nodes from 170 patients to evaluate sensitivity, specificity and concordance of the two methods. Additional analysis was done to investigate how cytokeratin 19 mRNA copy number affects prediction of non-sentinel node positivity. OSNA sensitivity was 93.2% and specificity 95.8%. Concordance between OSNA and histology was 95.6%. In the patients who had axillary clearance, the OSNA mRNA copy number on the sentinel node had 100% negative predictive value for histologically proven metastasis. mRNA copy numbers <1400 were not associated with histologically proven metastasis in subsequent nodes at axillary clearance. OSNA is a reliable method for the intra-operative evaluation of axillary lymph node metastasis even when half of the lymph node is used. Identification of mRNA copy number threshold predicting the positivity of non-sentinel axillary nodes seems to be feasible and would be clinically important.